Prospective, randomized, placebo-controlled, multicenter, double-blind, parallel-group, registration field trial evaluating izenivetmab, a caninized anti-nerve growth factor monoclonal antibody, administered quarterly to dogs with naturally occurring osteoarthritis

Izenivetmab, a caninized monoclonal antibody that targets nerve growth factor, was evaluated for osteoarthritis-related pain in a prospective, randomized, placebo-controlled, double-blind, parallel-group field trial, conducted at multiple private practices, enrolling 574 individually owned dogs (median age, 9.0 years) with osteoarthritis (e.g., moderate to nearly incapacitating). Dogs were block randomized (1:1) to izenivetmab ( n =289; 0.05-0.10 mg kg -1 ) or placebo (saline, n =285) administered subcutaneously every 3 months for a total duration of 9 months. Day 90 canine brief pain inventory (CBPI) treatment success (TS), the primary endpoint, required a pain interference score (PIS; 0-10) decrease of ≥2 and pain severity score (PSS; 0-10) decrease of ≥1. Izenivetmab showed significant ( p <0.05) improvement over placebo for CBPI TS (days 7-270). Of evaluable cases, day 90 CBPI TS (izenivetmab, n =255; placebo, n =257) rates were 36.3% and 21.4%, respectively ( p =0.0029); CBPI TS frequency 90 days after each dose was stable for both groups. Izenivetmab showed significant effect on all CBPI elements (PIS, PSS, quality of life) versus placebo. Several adverse events (e.g., polyuria, polydipsia, pain upon injection) occurred at a numerically higher frequency in the izenivetmab group versus placebo. Results demonstrated the safety and effectiveness of izenivetmab (0.05-0.10 mg kg -1 ) administered subcutaneously to dogs for osteoarthritis pain every three months for 9 months.